rs7996030

Variant names:

• chr13-28309200-A-G
• rs7996030
• NM_002019.4:c.3636-273T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002019.4(FLT1):​c.3636-273T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,120 control chromosomes in the GnomAD database, including 39,555 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (39555 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413
• Publications: 5 publications found

Genes affected

FLT1 (HGNC:3763): (fms related receptor tyrosine kinase 1) This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. This protein binds to VEGFR-A, VEGFR-B and placental growth factor and plays an important role in angiogenesis and vasculogenesis. Expression of this receptor is found in vascular endothelial cells, placental trophoblast cells and peripheral blood monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Isoforms include a full-length transmembrane receptor isoform and shortened, soluble isoforms. The soluble isoforms are associated with the onset of pre-eclampsia.[provided by RefSeq, May 2009]

ENSG00000307511 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.3636-273T>C		intron_variant	Intron 27 of 29	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.3636-273T>C		intron_variant	Intron 27 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105043 AN: 152002 Hom.: 39533 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.734

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.691 AC: 105103 AN: 152120 Hom.: 39555 Cov.: 32 AF XY: 0.701 AC XY: 52144 AN XY: 74368

African (AFR) AF: 0.366 AC: 15173 AN: 41484

American (AMR) AF: 0.821 AC: 12545 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2964 AN: 3468

East Asian (EAS) AF: 0.997 AC: 5142 AN: 5156

South Asian (SAS) AF: 0.896 AC: 4322 AN: 4824

European-Finnish (FIN) AF: 0.799 AC: 8468 AN: 10592

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54069 AN: 67992

Other (OTH) AF: 0.737 AC: 1556 AN: 2112

Alfa AF: 0.751 Hom.: 9005

Bravo AF: 0.676

Asia WGS AF: 0.919 AC: 3194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.76
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7996030; hg19: chr13-28883337;